Achilles Athanassiou

IL-1 Induces Vesicular Secretion of IL-6 without Degranulation from Human Mast Cells

FcεRI cross-linkage in mast cells results in release of granule-associated mediators, such as histamine and proteases, as well as the production of numerous cytokines, including IL-6. Mast cells have been increasingly implicated in inflammatory processes where explosive degranulation is not commonly observed. Here, we show that IL-1 stimulates secretion of IL-6 without release of the granule-associated protease tryptase in normal human umbilical cord blood-derived mast cells (hCBMCs). IL-6 secretion stimulated by IL-1 in hCBMCs is potentiated by priming with IL-4 and reflects the higher levels of IL-6 secreted from human leukemic mast cell line (HMC-1). Stimulating HMC-1 cells by both IL-1 and TNF-α results in synergistic secretion of IL-6. IL-6 is de novo synthesized, as its secretion is blocked by inhibitors of transcription or protein synthesis. IL-1 does not increase intracellular calcium ion levels in either hCBMCs or HMC-1 cells, and IL-6 stimulation proceeds in the absence of extracellular calcium ions. Ultrastructural Immunogold localization shows that IL-6 is excluded from the secretory granules and is compartmentalized in 40- to 80-nm vesicular structures. Selective secretion of IL-6 from mast cells appears distinct from degranulation and may contribute to the development of inflammation, where the importance of IL-6 has been recognized.

Azelastine Inhibits Secretion of IL-6, TNF-α and IL-8 as well as NF-κB Activation and Intracellular Calcium Ion Levels in Normal Human Mast Cells

Background: Mast cells are involved in allergic inflammation by secreting histamine, proteases and several cytokines, including interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-8. Certain histamine-1 receptor antagonists, such as azelastine present in the ophthalmic solution Optivar®, have been reported to inhibit histamine and tryptase secretion, but its effect on inflammatory cytokine release from normal human umbilical cord blood-derived cultured mast cells (hCBMC) are not well known. Methods: We investigated the effect of azelastine on the secretion of IL-6, TNF-α and IL-8 from hCBMC, as well as its possible mechanism of action. hCBMC sensitized with IgE were pretreated for 5 min with azelastine at 0.01, 0.1, 1, 3, 6, 12, 24, or 60 µM of Optivar®, before stimulation with anti-IgE for 6 h. Optivar® vehicle without azelastine was used as control. Cytokines were measured by ELISA, intracellular calcium levels by calcium indicators confocal, and nuclear factor-ĸB (NF-ĸB) by electromobility shift assay. Results: Stimulation with anti-IgE led to substantial secretion of IL-6, TNF-α and IL-8. Preincubation for 5 min resulted in almost maximal inhibition with 6 µM azelastine for TNF-α (80%), with 24 µM for IL-6 (83%) and 60 µM for IL-8 (99%); the vehicle solution at the same concentrations as Optivar® had no effect. Stimulation with anti-IgE increased intracellular Ca2+ level and induced NF-ĸB expression in hCBMC, which was inhibited by 24 µM azelastine. Conclusion: Azelastine inhibited hCBMC secretion of IL-6, TNF-α and IL-8, possibly by inhibiting intracellular Ca2+ ions and NF-ĸB activation. Azelastine may, therefore, be helpful in treating allergic inflammation.

Validation of fetal telemedicine as a new obstetric imaging technique

OBJECTIVE Our purpose was to establish whether obstetric ultrasonography interpreted by a live video telemedicine link is comparable to interpretation by videotape review in a low-risk patient population. STUDY DESIGN An Integrated Services Digital Network (ISDN 6) was established from three satellite offices to our central prenatal diagnostic center. Patients seen at these satellite offices had a complete fetal anatomic survey recorded onto videotape by a trained ultrasonographer. A live interactive video telemedicine link was then established to our center by the digital network, and a perinatologist directed the ultrasonographer through the anatomy survey. Subsequently a different perinatologist, blinded to the telemedicine interpretation, reviewed the videotaped examination. The reports from the videotaped and telemedicine scans were then compared on the basis of a score of 33 anatomic items. RESULTS The first 200 patients seen at the satellite offices were included. Telemedicine and videotape interpretations provided similar scores in 84% of scans. In 17 of the 33 anatomic categories telemedicine provided significantly better scores than videotape, whereas in the remaining 16 anatomic categories the scores were equivalent. More videotape than telemedicine examinations required repeat ultrasonography because of suboptimal imaging (10% vs 3%, p = 0.003). CONCLUSIONS The interpretation of obstetric ultrasonography with use of live video telemedicine is comparable to videotape review. Fetal telemedicine may prove to be a useful tool for providing ultrasonographic interpretation of fetal anatomy to a network of low-risk obstetric practices.

Limited Prognostic Value of a Staging System for Twin-to-Twin Transfusion Syndrome

Objective: Severe twin-to-twin transfusion syndrome (TTTS) is usually classified according to a staging system (I–V) based on ultrasonographic findings of polyhydramnios in the recipient, oligohydramnios in the donor, the presence or absence of the donor’s bladder, Doppler waveform changes and (impending) hydrops. Stage correlates with the severity of disease, and it is assumed that, without intervention, severe TTTS will evolve in succession from stage I to stage V (fetal demise). However, this progression has not been validated in longitudinal studies. Herein, we report on the natural progression of severe TTTS in a cohort of patients from a regional Fetal Treatment Program. Methods: Eighteen patients with severe TTTS, diagnosed between 15 and 25 weeks of gestation, were managed over a 28-month period. Data were collected until delivery, endoscopic surgical intervention or dual fetal demise. Patients were evaluated at least once a week. Stage, estimated fetal weight, percent recipient/donor body weight discordance and survival were recorded. Results: The present study represents a total follow-up of 108 patient-weeks. Of 90 week-to-week evaluations, 65 showed no change in stage; 11 showed downstaging (by more than 1 stage in 3, or 27%), and 13 showed upstaging (by more than 1 stage in 8, or 62%). Nine patients (all stage II or above) underwent endoscopic laser ablation. Overall survival was 67%, and survival of at least 1 twin occurred in 78% of pregnancies. Weight discordance between the donor and recipient did not predict outcome. Conclusion: The current staging system for severe TTTS may not be helpful in predicting the direction, degree or speed of progression of the condition. Indications for intervention should remain stage-related, and not based on projected progression.

Liver Masses in Pregnancy

Liver masses in pregnancy are rare but when encountered pose a difficult clinical scenario with many diagnostic and management uncertainties. They can be classified as nonneoplastic and neoplastic and further subdivided into benign and malignant. Fortunately, benign hepatic adenomas, focal nodular hyperplasia, and hemangiomas appear to be the more common sources of liver masses identified in this generally young and healthy patient population, but the actual incidence of each type is unknown during pregnancy. In some areas of the world infectious causes are more prevalent. Malignant causes of hepatic masses carry a grave prognosis, similar to that for the nonpregnant population. The clinical presentation of a liver mass during pregnancy is similar in presentation to a nonpregnant patient, although symptoms may initially be attributed to pregnancy, and diagnosis is therefore delayed. Management varies depending on the etiology and size of the mass and on gestational age.

Impact of gestational age at delivery on the economics of triplet pregnancy

OBJECTIVE To establish the charges associated with triplet pregnancies managed at a single tertiary center, over a 5-year time period, and to evaluate the impact of prematurity on these charges. METHODS All triplet pregnancies that reached at least 20 weeks gestation and received prenatal and neonatal care at our center from 1992 to 1996 were included. Charges for these mothers and neonates were extracted from two separate hospital billing computer systems, encompassing all inpatient, outpatient, technical, and professional charges. Linear regression was used to evaluate the relationship between gestational age at delivery and total charges. RESULTS Fifty-five triplet pregnancies were included, resulting in the admission of 149 liveborn neonates. The median gestational age at delivery was 32.1 weeks. The mean charges per triplet mother were:

Validation of first-trimester telemedicine as an obstetric imaging technology : A feasibility study

6,899 (professional),

Corticotropin-Releasing Hormone and Its Structurally Related Urocortin Are Synthesized and Secreted by Human Mast Cells

3,959 (hospital outpatient), and

Maternal Morbidity Associated with Triplet Pregnancy

32,686 (hospital inpatient). The mean charges per neonatal sibling set were:

Maternal and Neonatal Outcome of 100 Consecutive Triplet Pregnancies

20,107 (professional) and